Gene abnormalities have now been demonstrated to be responsible for the pathogenesis of a number of types of congenital heart disease. Thus, the proposed Children's Hospital of Philadelphia (CHOP) SCCOR program is based on the following working hypothesis: Basic discoveries concerning gene abnormalities and related patterns of gene expression can be applied to a unifying approach for both understanding the complex basis for cardiac dysmorphogenesis as well as providing therapeutic insights for translational directions. Strong prior collaborations with major discoveries concerning the genetic basis of congenital heart disease will facilitate the activities of this SCCOR, and these include ten years of productivity in the concluding SCOR programs, with continuing Clinical and Cell Culture/DNA Cores, and continuing Core Directors. These Cores have also been resources for both national and international collaborations. Previous collaborations among the Key Personnel have produced more than 150 publications over the past decade. The SCCOR will be based in CHOP's Cardiac Center, which was recently ranked first in the nation for cardiac care by Child magazine based on JCAHO evaluations. The objectives of the program may be summarized as follows: Project 1 (basic) will investigate novel heterograft biomaterials for use in congenital heart surgery, emphasizing cellular and molecular mechanisms that affect biocompatibility. Project 2 (clinical) will continue its work from the SCOR on outflow tract malformations and its objective is to assess the contribution and relative risk of specific genes involved in cardiac development in cardiac patients using family-based genetic association studies, and directions based on gene interactions and complex associations. The Project 3 (clinical) objectives relate discoveries of gene abnormalities associated with congenital heart defects to cardiac outcomes. Project 4 (clinical) will investigate clinical cytogenetics discoveries revealing new relationships to mechanisms of cardiac dysmorphogenesis that are associated with gene deletions in the subtelomere regions. Project 5 (clinical) will investigate the novel association of chromosomal translocation break point gene abnormalities with congenital heart disease. The Projects will be supported by six cores: Administrative; Clinical Skills Development; Clinical; Cell Culture and DNA Analysis; Cardiac Morphology, Gene Expression, and Histology; and Bioinformatics and Data Analysis.